What is the recommended dose of St. John's Wort?

- **Depression:** 300mg 3x/day standardized to 0.3% hypericin (or 3-5% hyperforin) - **WS 5570 / WS 5572 (branded):** Most studied extracts - **LI 160:** 300mg 3x/day - **Duration:** 4-6 weeks mini...

Is St. John's Wort safe to take daily?

St. John's Wort is rated "Prescription Interactions" based on clinical evidence. - Photosensitivity (fair-skinned individuals — wear sunscreen) - GI upset, dizziness, confusion - Vivid dreams, restlessness - Dry mouth

Does St. John's Wort interact with any medications?

St. John's Wort has 14 known drug interactions, including interactions with SSRIs / SNRIs (all), Oral contraceptives, Cyclosporine / tacrolimus. Check with your doctor before combining with prescription medications.

LOADINGLoading your Pro surface...

Ingredient Research

Graded against 173,636 supplements + 177 published clinical interactions, sourced from PubMed, FDA CAERS, openFDA, NIH DSLD

St. John's Wort

STRONG EVIDENCESupplementLast updated April 2026

SCAN DOSE SUMMARY

St. John's Wort is one of the most evidence-backed herbal antidepressants — comparable to SSRIs for mild-to-moderate depression in multiple meta-analyses. Our research also identifies it as the MOST DANGEROUS supplement for drug interactions in our entire database. It's a potent CYP3A4 inducer that reduces the effectiveness of birth control, HIV medications, organ transplant drugs, and dozens of other medications. It should never be combined with prescription antidepressants.

EVIDENCE GRADES

Mild-to-moderate depressionStrong — Cochrane review of 29 RCTs (PMID: 18843608)

Severe depressionNegative — not effective for severe MDD

C-

AnxietyLimited direct evidence; secondary to depression improvement

C+

Menopausal symptomsSmall positive trials

ADHDVery preliminary

OPTIMAL DOSAGE

Depression: 300mg 3x/day standardized to 0.3% hypericin (or 3-5% hyperforin)
WS 5570 / WS 5572 (branded): Most studied extracts
LI 160: 300mg 3x/day
Duration: 4-6 weeks minimum for antidepressant effect
Standardization: Hypericin was originally thought to be the active compound; hyperforin is now considered more important for antidepressant action

Scan a supplement containing St. John's Wort

DRUG INTERACTIONS

SSRIs / SNRIs (all)Severe

Serotonin syndrome risk + CYP-mediated interaction

Oral contraceptivesSevere

CYP3A4 induction REDUCES hormone levels → breakthrough bleeding → PREGNANCY

Cyclosporine / tacrolimusSevere

CYP3A4 induction → organ transplant REJECTION (documented cases)

HIV protease inhibitors (indinavir)Severe

Reduces drug levels by 50-80% → treatment failure

WarfarinSevere

CYP induction reduces warfarin levels → clotting risk

DigoxinSevere

P-gp induction reduces digoxin levels

Statins (simvastatin, atorvastatin)Moderate

CYP3A4 induction reduces statin levels

Benzodiazepines (alprazolam, midazolam)Moderate

CYP3A4 induction reduces levels

Chemotherapy drugsSevere

Reduces drug levels — treatment failure risk

MethadoneSevere

Reduced levels → withdrawal symptoms

Triptans (sumatriptan)Severe

Serotonin syndrome risk

TheophyllineModerate

Reduced levels

Omeprazole (PPI)Moderate

CYP2C19 induction reduces levels

Irinotecan (chemo)Severe

Reduces SN-38 levels by 42%

SAFETY PROFILE

⚠️ MOST DRUG INTERACTIONS OF ANY SUPPLEMENT

St. John's Wort is a POTENT inducer of CYP3A4, CYP2C9, CYP2C19, CYP1A2, and P-glycoprotein. This means it DECREASES blood levels of dozens of medications. This is not theoretical — these interactions have caused treatment failures, organ transplant rejections, and unintended pregnancies.

Drug Interactions

Side Effects

Photosensitivity (fair-skinned individuals — wear sunscreen)
GI upset, dizziness, confusion
Vivid dreams, restlessness
Dry mouth

Pregnancy & Lactation

AVOID — CYP induction affects many medications; limited direct pregnancy safety data; may reduce effectiveness of any co-administered drugs

WADA Status

Not Prohibited

HOW SCAN DOSE SCORES THIS

THE HIGHEST INTERACTION RISK SUPPLEMENT IN OUR DATABASE

If ANY prescription medication is in the user's profile, St. John's Wort must trigger a comprehensive drug interaction review

Birth control users: automatic SEVERE warning (documented pregnancy risk)

SSRI/SNRI users: automatic CONTRAINDICATED alert

Transplant patients: absolute contraindication

Products should carry prominent drug interaction warnings — score penalty for products that don't

For users on NO medications with mild-to-moderate depression: legitimate option with strong evidence

CLINICAL REFERENCES

Linde K et al. St John's wort for major depression. *Cochrane Database Syst Rev.* 2008.

(2008). PMID: 18843608

Markowitz JS et al. Effect of St John's wort on drug metabolism by induction of CYP3A4.

PMID: 10789117

Ruschitzka F et al. Acute heart transplant rejection due to Saint John's wort. *Lancet.* 2000.

(2000). PMID: 10861149

Piscitelli SC et al. Indinavir concentrations and St John's wort. *Lancet.* 2000.

(2000). PMID: 12622848

RELATED RESEARCH

Acacia Fiber

Activated Charcoal

Agave Inulin

Agmatine SulfateReduced neuropathic pain by 46.1%

Scan Your St. John's Wort Supplement Browse all ingredients

Independently graded against 173,636 indexed supplements with 177 published clinical interactions, sourced from PubMed, FDA CAERS, openFDA, and NIH DSLD | Last updated: April 2026

Not medical advice. Based on published clinical research and systematic reviews.

Safety

St. John's Wort: Drug Interactions

The most interaction-prone supplement in common use. St. John's Wort induces multiple drug-metabolism enzymes and can cause treatment failure across many drug classes.

Mechanism: St. John's Wort is a potent inducer of CYP3A4, CYP2C9, CYP1A2, and P-glycoprotein. It reduces the blood levels of almost every drug metabolized by these enzymes.

Discuss with prescriber

Clinically significant interactions per published research. Talk to your prescriber or pharmacist before using this supplement if you take any of these.

SSRIs (Prozac, Zoloft, Lexapro)
Additive serotonergic effect.
RiskSerotonin syndrome, potentially fatal.
ActionNever combine.
SourcePMID: 27444983
SNRIs (Effexor, Cymbalta)
Additive serotonergic effect.
RiskSerotonin syndrome.
ActionNever combine.
SourceFDA warning
Oral contraceptives
Induces CYP3A4, accelerating estrogen metabolism.
RiskUnplanned pregnancy from contraceptive failure.
ActionNever combine. Use backup contraception.
SourcePMID: 19719333
Cyclosporine
Induces CYP3A4, dramatically reducing cyclosporine levels.
RiskOrgan rejection in transplant patients.
ActionAbsolutely never combine.
SourceFDA black box warning
HIV protease inhibitors (ritonavir, indinavir)
Induces CYP3A4, reducing drug levels.
RiskTreatment failure and viral rebound.
ActionNever combine.
SourceFDA warning
Warfarin
Induces CYP enzymes, reducing warfarin levels.
RiskBlood clots from subtherapeutic INR.
ActionNever combine.
SourcePMID: 19719333
Digoxin
Induces P-glycoprotein, reducing digoxin levels.
RiskHeart failure from subtherapeutic levels.
ActionNever combine.
SourceClinical pharmacology
Chemotherapy agents
Induces CYP3A4, reducing drug levels.
RiskTreatment failure.
ActionNever combine.
SourceFDA warning
Theophylline
Induces CYP1A2, reducing levels.
RiskLoss of asthma or COPD control.
ActionAvoid.
SourceClinical pharmacology
Triptans (sumatriptan)
Additive serotonergic effect.
RiskSerotonin syndrome risk.
ActionAvoid.
SourceFDA warning

Stop 2 weeks before surgery

Anesthesia interactions from CYP enzyme induction.

Educational information only. This is not medical advice. These statements have not been evaluated by the FDA. Talk to your prescriber before starting, stopping, or combining any supplement with prescription medication.

Discover More

Explore

Browse All 834 Ingredients Browse All 20 Conditions